2009-2010 Pilot Project Awards

The awardees and their projects are:

 

Principal Investigator

Project Title/Brief Description

 
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Don Coltart, PhD
Assistant Professor of Chemistry
Synthesis and Biological Evaluation of Single Enantiomer Forms of the Anti-Malarial Mefloquine and Related Compounds

Mefloquine is an anti-malarial drug developed by the U.S. Army that is routinely administered to troops serving overseas and prescribed to millions of tourists and world travelers. While highly effective as an anti-malarial, mefloquine causes serious side effects.

   

Mefloquine was developed as a racemic mixture of the (+) and (–) enantiomers of the molecule. Research suggests that the administration of pure (+)-enantiomer would presumably alleviate side effects, while retaining anti-malarial properties. This project will use a simple, cost effective method using n-amino cyclic carbamate (ACC) auxiliaries to synthesize mefloquine into pure form of its two enantiomers, The anti-malarial properties of each will be evaluated in an in vitro assay, cell-based growth inhibition study, and a small animal model.

 

Co-Investigators:

  • Tim Haystead, PhD, Associate Professor of Pharmacology and Cancer Biology
  • J. Brice Weinberg, MD, Professor of Medicine in the Division of Hematology
 
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Charles Michael Cotten, MD, MHS
Associate Professor of Pediatrics
Autologous Cord Blood Cells for Brain Injury in Term Newborns

Three thousand infants die or develop cerebral palsy annually in the U.S. due to hypoxic-ischemic encephalopathy caused by perinatal asphyxia. In hypoxic-ischemic encephalopathy animal models, umbilical cord blood collected at birth and given back as cell infusions in the days after birth reduces brain injury and improves outcomes.

   

This project will study the effects of autologous umbilical cord blood collected from the placenta of term neonates born with hypoxic encephalopathy. The reinfusion of the cord blood in increments will be added to the current post-natal whole body cooling regimen that is currently standard of care. Subjects will be monitored with radiological structural and developmental tests to evaluate effects.

 

Co-Investigators:

  • Ricki Goldstein, MD, Associate Professor of Pediatrics
  • Ron Goldberg, MD, Professor of Pediatrics
  • James Provenzale, MD, Professor of Radiology
  • Joanne Kurtzberg, MD, Professor of Pediatrics and Pathology, Director Pediatric Blood and Marrow Transplant Program, Director, Carolinas Cord Blood Bank
  • Allen Song, PhD, Professor and Director, Brain Imaging and Analysis Center
 
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David (Shiaowen) Hsu, MD
Medical Instructor in Department of Medicine, Division of Medical Oncology
Development of a Paraffin Base Assay to Predict Patients with Early Stage Colorectal Cancer at High Risk for Recurrence

Colorectal cancer is the second leading cause of cancer death in the U.S. The long-term goal of this project is to identify patients at high risk for disease recurrence and improve treatment in patients diagnosed with early stage colorectal cancer.

   

The current challenge is to identify patients who are most likely to benefit from adjuvant treatment as well as optimizing the current adjuvant regimens. A genomic base signature has been developed that can identify patients with early stage colorectal cancer who are at high risk for recurrence. This project will advance the development of a multi-gene expression assay with formalin-fixed tumor samples to estimate disease recurrence and response to drug therapy following surgery for Stage 2 colorectal cancer.

 

Co-Investigator:

  • Herbert Hurwitz, MD, Associate Professor of Medicine in Division of Medical Oncology
 
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Christopher D. Kontos, MD
Associate Professor of Cardiovascular Medicine
PTEN Gene Therapy for the Prevention of Vein Graft Disease

Autologous veins are the most commonly used conduits for bypass grafting in coronary and peripheral artery disease and for creation of arteriovenous fistulas (AVFs) for hemodialysis.

   

The utility of these conduits is compromised by high rates of occlusive vein graft disease, resulting in substantial morbidity and cost.The investigators have developed a novel and promising approach to prevent vein graft failure that utilizes adeno-associated virus (AAV)-mediated gene delivery of the lipid phosphatase PTEN. This project will validate the efficacy of AAV-PTEN in a small animal model and to demonstrate its safety.

 

Co-Investigators:

  • Carmelo Milano, MD, Associate Professor of Cardiothoracic Surgery
  • Dawn Bowles, PhD, Assistant Professor of Cardiothoracic Surgery
 
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Paul Kuo, MD
Professor of Surgery
Osteopontin Aptamer Inhibits Breast Cancer Metastasis

Osteopontin (OPN) is a secreted tumor protein which plays a central role in breast cancer metastasis, the principle cause of death among breast cancer patients. Because it is accessible in the extracellular space, OPN is an ideal therapeutic target.

   

This project will characterize the pharmacokinetic and pharmacodynamic characteristics of an RNA aptamer capable of blocking OPN-mediated metastasis by binding and sequestering secreted extracellular OPN. This data will be used to optimize dosing in an in vivo model of metastatic human breast cancer.

 

Co-Investigator:

  • Rebekah White, MD, Assistant Professor of Surgery
 
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Duane A. Mitchell, MD
Assistant Professor of Neurosurgery
Clinical Development of a Therapeutic Vaccine Targeting CMV Antigens in Glioblastoma

Glioblastoma multiforme (GBM) is the most common and most aggressive type of primary brain tumor in humans. It has recently been discovered that majority of GBMs (>90%) are associated with tumor-restricted reactivation of human cytomegalovirus (CMV).

   

This project will perform the preclinical investigations of immunodominant CMV antigen proteins. The investigators plan to acquire sufficient feasibility and toxicity data for FDA and IRB approval of a Phase I clinical trial evaluating the safety and immunologic effects of CMV peptide vaccines in patients with newly-diagnosed GBM.

 

Co-Investigators:

  • John Sampson, MD, Associate Professor of Neurosurgery
  • James Herndon, PhD, Associate Professor, Department of Biostatistics and Bioinformatics
  • Kent Weinhold, PhD, Professor of Immunology and Surgery
  • David Reardon, MD, Associate Professor of Neurosurgery
 
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Edward Patz, MD
Professor Chest Radiology
Novel Serum Biomarkers for the Early Detection of Lung Cancer

Lung cancer is the most common cancer in the U.S. Current early detection strategies are inadequate, and improved methods for early lung cancer diagnosis could have an important impact on clinical management and patient outcome.

   

This project will focus on the development of a protein microarray that measures autoantibodies in plasma for diagnosis of non-small cell lung cancer (NSCLC) as an adjunct to imaging prior to obtaining a lung tumor biopsy.

 

Co-Investigators:

  • Michael Campa, PhD, Associate Professor in Radiology
  • Elizabeth Gottlin, PhD, Assistant Professor in Radiology
 
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David S. Warner, MD
Professor of Anesthesiology
Intravenously Bioavailable MnPorphryin for Treatment of Ischemic Stroke

This project will examine the use and effectiveness of a novel MnPorphyrin to attenuate brain damage due to ischemia-related oxidative stress. This novel MnPorphryin scavenges oxygen-based free radicals with high efficiency and has been chemically engineered to penetrate the blood-brain barrier (BBB).

   

The overall goal is to optimize the intravenous dosing, formally define pharmacokinetics and toxicity, and conduct a long-term outcome analysis of this MnPorphyrin treatment providing definitive proof of clinically relevant efficacy.

 

Co-Investigators:

  • Huaxin Sheng, MD, Associate Professor in Anesthesiology
  • Ines Batinic-Haberle, PhD, Professor in Radiation Oncology